Vitamin K1 mediates the postribosomal structural completion of the critical blood coagulation factors II (prothrombin), VII, IX and X to biologically active forms by mechanisms which have not been fully elucidated. Warfarin, a widely employed human oral anticoagulant and rodenticide, antagonizes vitamin K1 dependent processes by mechanisms which also have not been unambiguously defined. A comprehensive in vitro investigation of R and S warfarin metabolism by hepatic cytochromes P-450 of noninduced rats and rats induced by various xenobiotic agents has been undertaken. Pharmacokinetic studies of R and S warfarin in rats administered the agents which cause the most pronounced alterations in normal rates of metabolism and metabolite profiles have also been undertaken and are being correlated with antivitamin K1 activity. Investigations of the in vitro metabolism of R and S warfarin in variously induced rats have demonstrated their utility as probes of the multiplicity of the hepatic cytochromes P-450 and have revealed the existence of a microsomal enzyme system responsible for the stereospecific reduction of S-warfarin in adult rats. Collectively the results of these investigations will provide further insight into the general mechanisms of warfarin mediated vitamin K1 antagonism as well as those of microsomal drug metabolism.